Panax ginseng C. A. Meyer (Araliaceae), is one of the medicinal plants that have long been used for treating various diseases in Asian countries, including China, Korea, and Japan. In particular, ginsenosides (ginseng saponin), the main active ingredient of Panax ginseng, are known to have various physiological activities, such as anti-aging activity, anti-inflammatory activity, antioxidant activities in the central nervous system, cardiovascular system, and the immune system (Wu et al., J. Immunol., 148:1519-25, 1992; Lee, Facts about Ginseng, the Elixir of Life., Hollyn International. New Jersey, 1992; Huang, The Pharmacology of Chinese Herbs. CRC Press. Florida, 1999), anti-diabetic activity (Chang, Pharmacology and Application of Chinese Material Medica. Vol. 1, World Scientific. Singapore, 1986), and anti-tumor activity (Sato et al., Biol. Pharm. Bull. 17:635-9, 1994; Mochizuki et al., Biol. Pharm. Bull. 18:1197-1202, 1995).
Further, ginsenosides are metabolized by bacteria inside the human intestine after intake, where their metabolites are known to have various physiological activities (Karikura et al., Chem. Pharm. Bull., 39:2357-61, 1991; Kanaoda et al., J. Tradit. Med. 11:241-5, 1994; Akao et al., Biol. Pharm. Bull., 21:245-9, 1998). For example, Rb1, Rb2, and Rc, which are protopanaxadiol-type ginsenosides, are metabolized by human intestinal bacteria into IH-901 (20-O-β-D-glucopyranosyl-20(S)-protopandaxadiol) (Hasegawa et al., Planta Medica 63:463-40, 1997; Tawab et al., Drug Metab. Dispos., 31:1065-71, 2003), while Re and Rg1, protopanaxatriol-type ginsenosides, are metabolized into ginsenoside Rh1 or ginsenoside F1 (Hasegawa et al., Planta Medica 63:463-40, 1997; Tawab et al., Drug Metab. Dispos., 31:1065-71, 2003), where the metabolites IH-901, Rh1, and F1 exhibit various physiological activities.
Specifically, IH-901 is generally known for its anti-diabetic (Choi et al., J. Ginseng Res. 31(2): 79-85, 2007) and immune-enhancing activities. Further, IH-901 is known to induce an anti-metastasis or anti-cancer effect by blocking tumor invasion or preventing chromosomal mutation and tumor formation (Wakabayashi et al., Oncol. Res., 9:411-7, 1998; Lee et al., Cancer Lett., 144:39-43, 1999).
Several researchers have tried to produce genuine prosapogenin or sapogenin by using methods, such as chemical synthesis, subacid hydrolysis, and alkali digestion (Han et al., Planta Medica 44:146-9, 1982; Chen et al., Chem. Pharm. Bull. 35:1653-5, 1987; Elyakov et al., Synthesis of the Ginseng Glycosides and Their Analogs. Proc. 6th Int. Ginseng Symp. Seoul 74-83, 1993). However, the above methods are known to cause various side reactions, such as epimerization, hydration, and hydroxylation.
Thus, a number of methods that convert ginsenosides under mild conditions by utilizing enzymes (Ko et al., Biosci. Biotechnol. Biochem. 64:2739-43, 2000; Ko et al., Planta Med. 69:285-6, 2003) or intestinal bacteria (Hasegawa et al., Planta Medica 63:463-40, 1997; Bae et al., J. Microbial. Biotechnol. 13:9-14, 2003) have been studied. Specifically, methods for preparing IH-901 by hydrolyzing diol-type ginsenosides with naringinase, as well as methods for preparing IH-901 by administrating the diol-type ginsenosides orally to a rat and then having them digested in the colon have been developed. However, the above preparation methods were found to have certain drawbacks in that the production yield of IH-901 is extremely low and various secondary metabolites are produced, making it difficult to obtain highly pure IH-901 (Karikura et al., Chem. Pharm. Bull. 38:2859, 1990).
More recently, other methods for preparing IH-901 by reacting a variety of enzymes with ginsenosides (Korean Laid-open Patent Publication No. 2003-94757; Korean Patent Nos. 418604 and 377546) have been studied, but the amount of IH-901 produced using these methods was found to be too low to have any significant effect. Further, the above methods involve complicated steps and are unsuitable for preparing a fermented ginseng concentrate having a high content of IH-901.
The present invention is directed to overcoming these deficiencies in the art.